A chemical genomic approach identifies matrix metalloproteinases as playing an essential and specific role in Xenopus melanophore migration.

Autor: Tomlinson ML; School of Biological Sciences, University of East Anglia, Norwich, UK., Guan P, Morris RJ, Fidock MD, Rejzek M, Garcia-Morales C, Field RA, Wheeler GN
Jazyk: angličtina
Zdroj: Chemistry & biology [Chem Biol] 2009 Jan 30; Vol. 16 (1), pp. 93-104.
DOI: 10.1016/j.chembiol.2008.12.005
Abstrakt: To dissect the function of matrix metalloproteinases (MMPs) involved in cellular migration in vivo, we undertook both a forward chemical genomic screen and a functional approach to discover modulators of melanophore (pigment cell) migration in Xenopus laevis. We identified the 8-quinolinol derivative NSC 84093 as affecting melanophore migration in the developing embryo and have shown it to act as a MMP inhibitor. Potential targets of NSC 84093 investigated include MMP-14 and MMP-2. MMP-14 is expressed in migrating neural crest cells from which melanophores are derived. MMP-2 is expressed at the relevant time of development and in a pattern that suggests it contributes to melanophore migration. Morpholino-mediated knockdown of both MMPs demonstrates they play a key role in melanophore migration and partially phenocopy the effect of NSC 84093.
Databáze: MEDLINE